Highlights
- •High-risk smoldering presents a 50% progression risk to active myeloma at 2 years.
- •Early treatment has demonstrated to delay the progression to myeloma.
- •Rd confirms the sustained benefit in TTP and OS in high-risk smoldering.
- •Many trials are ongoing to support the role of early detection and intervention.
Abstract
Background
Smoldering multiple myeloma (SMM) is a heterogeneous disease in terms of progression
to myeloma (MM), but its standard of care continues to be observation.
Methods
The QuiRedex phase 3 trial initiated in 2007 included 119 high-risk patients with
SMM randomized to treatment or observation. Treatment consisted of nine 4-week induction
cycles (lenalidomide [Rd], 25 mg on days 1–21 plus dexamethasone, 20 mg on days 1–4
and 12–15), followed by maintenance (R, 10 mg on days 1–21) for up to 2 years. The
primary end-point was time to progression (TTP) to myeloma based on per protocol population.
Secondary end-points were overall survival (OS), response rate, and safety. An update
of the trial after a long-term follow-up is presented here. This trial was registered
with ClinicalTrials.gov (NCT00480363).
Findings
After a median follow-up time of 12.5 years (range: 10.4–13.6), the median TTP to
MM was 2.1 years in the observation arm and 9.5 years in the Rd arm (HR: 0.28, 95%
CI: 0.18–0.44, p < 0.0001). The median OS was 8.5 years in the abstention arm and
not reached in the Rd group (HR: 0.57, 95% CI: 0.34–0.95, p = 0.032). Patients who
progressed received optimized treatments according to the standards of care, and the
OS from progression was comparable in both arms (p = 0.96).
Interpretation
This analysis confirms that early treatment with Rd for high-risk SMM translates into
a sustained benefit in both TTP and OS.
Funding
Pethema (Spanish Program for the Treatment of Hematologic Diseases), Spain.
Keywords
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Article info
Publication history
Published online: September 03, 2022
Accepted:
July 26,
2022
Received in revised form:
July 23,
2022
Received:
May 29,
2022
Footnotes
☆Presented as abstract at the 25th European Hematology Association Congress in June 2020.
Identification
Copyright
© 2022 Elsevier Ltd. All rights reserved.
